Showing papers in "Journal of Organic Chemistry in 2018"
TL;DR: Both the three-component and the two-component cyclization/cross-coupling processes will be reviewed with a focus on strategies utilized to overcome the complications of β-hydride elimination from Heck C(sp3)-[M] intermediates, which usually functions as a major side reaction.
Abstract: The use of combined Heck carbometalation and cross-coupling remains one of the most powerful ways for the difunctionalization of unactivated olefins with organometallic reagents and organohalides. This synopsis will provide an overview of this reaction developed in the last three and a half decades. Herein, both the three-component and the two-component cyclization/cross-coupling processes will be reviewed with a focus on strategies utilized to overcome the complications of β-hydride elimination from Heck C(sp3)-[M] intermediates, which usually functions as a major side reaction.
205 citations
TL;DR: This work presents a selective synthesis of 2-substituted and 1,2-disubstituting benzimidazoles by acceptorless dehydrogenative coupling of aromatic diamine with primary alcohols by phosphine-free tridentate NNS ligand-derived manganese(I) complex.
Abstract: Herein, we present a selective synthesis of 2-substituted and 1,2-disubstituted benzimidazoles by acceptorless dehydrogenative coupling of aromatic diamine with primary alcohols. The reaction is catalyzed by a phosphine-free tridentate NNS ligand-derived manganese(I) complex.
109 citations
TL;DR: An improved, one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides, enabling late-stage functionalization, which is of high interest to medicinal chemistry.
Abstract: An improved, one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides. The conditions employed are mild, demonstrate a high degree of functional group tolerance, and do not require a large excess of the carboxylic acid reactant. As a result, this reaction can be applied to drug-like scaffolds and molecules with sensitive functional groups, enabling late-stage functionalization, which is of high interest to medicinal chemistry.
106 citations
TL;DR: Regioselective halogenation of arenes and heterocycles with N-halosuccinimides in fluorinated alcohols is disclosed and a wide diversity of halogenated arenes are obtained in good yields with high regioselectedivity.
Abstract: Regioselective halogenation of arenes and heterocycles with N-halosuccinimides in fluorinated alcohols is disclosed. Under mild condition reactions, a wide diversity of halogenated arenes are obtained in good yields with high regioselectivity. Additionally, the versatility of the method is demonstrated by the development of one-pot sequential halogenation and halogenation-Suzuki cross-coupling reactions.
102 citations
TL;DR: A chiral phosphoric acid-catalyzed approach constructing dihydrocoumarin motifs by the addition of azlactones to para-quinone methides (p-QMs) was developed and two possible pathways were proposed to explain the stereoselectivity.
Abstract: A chiral phosphoric acid-catalyzed approach constructing dihydrocoumarin motifs by the addition of azlactones to para-quinone methides (p-QMs) was developed. The reaction proceeded smoothly with a wide range of p-QMs and azlactones to generate corresponding products in high yields with excellent diastereoselectivities (>19:1 dr) and enantioselectivities (up to 99% ee). Two possible pathways were proposed to explain the stereoselectivity.
99 citations
TL;DR: This strategy enables highly selective difunctionalization of imidazo[1,2-a]pyridine to access sulfones and sulfides in good yields and indicates a radical pathway involved in the reaction mechanisms.
Abstract: Novel iodine-induced sulfonylation and sulfenylation of imidazopyridines have been described using sodium sulfinates as the sulfur source. This strategy enables highly selective difunctionalization of imidazo[1,2-a]pyridine to access sulfones and sulfides in good yields. A wide range of substrates and functional groups were well-tolerated under optimized conditions. Moreover, control experiments have been conducted, indicating a radical pathway involved in the reaction mechanisms.
97 citations
TL;DR: This study reports a nickel-catalyzed sustainable synthesis of polysubstituted quinolines from α-2-aminoaryl alcohols by a sequential dehydrogenation and condensation process that offers the advantages of a low catalyst loading and wide substrate scope.
Abstract: This study reports a nickel-catalyzed sustainable synthesis of polysubstituted quinolines from α-2-aminoaryl alcohols by a sequential dehydrogenation and condensation process that offers the advantages of a low catalyst loading and wide substrate scope. In contrast to earlier reported methods, this strategy allows the use of both primary as well as secondary α-2-aminoaryl alcohols in combination with either ketones or secondary alcohols for desired product formation. Using this methodology, 30 substituted quinoline derivatives were synthesized with up to 93% isolated yields.
94 citations
TL;DR: The present MEDT study provides an explanation for the unexpected ortho regioselectivity experimentally found in the 32CA reactions involving weak electrophilic ethylenes such as ethyl acrylate and acrylonitrile.
Abstract: The zw-type [3 + 2] cycloaddition (32CA) reactions of C,N-dialkyl nitrones with a series of ethylenes of increased electrophilic character have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Both, reactivity and selectivities are rationalized depending on the polar character of the reaction. Due to the strong nucleophilic character of C,N-dialkyl nitrones, the corresponding zw-type 32CA reactions are accelerated with the increased electrophilic character of the ethylene, which also plays a crucial role in the reaction mechanism, thus determining the regio- and stereoselectivities experimentally observed. While, in the 32CA reactions with nucleophilic ethylenes, the reaction begins with the formation of the C–C single bond, determining the ortho regioselectivity, in the 32CA reactions with strong electrophilic ethylenes, the reaction begins with the formation of the C–O single bond involving the β-conjugated carbon of the ethylene, determinin...
85 citations
TL;DR: This facile protocol provided an efficient approach to a variety of cyanoalkylated oxindoles and dihydroquinolin-2(1H)-ones with a broad substrate scope and excellent functional group tolerance.
Abstract: The copper-catalyzed cyclization of activated alkenes with cyclobutanone O-acyl oximes under redox-neutral conditions has been reported. This facile protocol provided an efficient approach to a variety of cyanoalkylated oxindoles and dihydroquinolin-2(1H)-ones with a broad substrate scope and excellent functional group tolerance. In this reaction, sequential C–C bond cleavage, radical addition, and cyclization processes were involved, wherein multiple bonds were constructed in a one-pot reaction. Mechanistic studies suggest that the reaction probably proceeded via a radical pathway.
84 citations
TL;DR: The rhodium(III)-catalyzed C-H functionalization followed by intramolecular annulation reactions between azobenzenes and sulfoxonium ylides is described, leading to the efficient formation of 3-acyl (2 H)-indazoles with a range of substrate scope.
Abstract: The rhodium(III)-catalyzed C–H functionalization followed by intramolecular annulation reactions between azobenzenes and sulfoxonium ylides is described. This protocol leads to the efficient formation of 3-acyl (2H)-indazoles with a range of substrate scope. A high level of chemoselectivity and functional group tolerance of this transformation were also observed.
83 citations
TL;DR: A metal-free visible-light-induced phosphonylation of 2 H-indazoles with diphenylphosphine oxide has been developed using rose bengal as an organophotoredox catalyst under ambient air at room temperature and the experimental result suggests the radical pathway of the reaction.
Abstract: A metal-free visible-light-induced phosphonylation of 2H-indazoles with diphenylphosphine oxide has been developed using rose bengal as an organophotoredox catalyst under ambient air at room temperature. A library of diphenyl(2-phenyl-2H-indazol-3-yl)phosphine oxide with broad functionalities has been synthesized in high yields. The experimental result suggests the radical pathway of the reaction.
TL;DR: This contribution is the first example of a multistep synthesis where all discrete steps were optimized with an autonomous flow reactor and allows fast and efficient optimizations of the chemical steps leading to carpanone.
Abstract: A modular autonomous flow reactor combining monitoring technologies with a feedback algorithm is presented for the synthesis of the natural product carpanone. The autonomous self-optimizing system, controlled via MATLAB, was designed as a flexible platform enabling an adaptation of the experimental setup to the specificity of the chemical transformation to be optimized. The reaction monitoring uses either online high pressure liquid chromatography (HPLC) or in-line benchtop nuclear magnetic resonance (NMR) spectroscopy. The custom-made optimization algorithm derived from the Nelder–Mead and golden section search methods performs constrained optimizations of black-box functions in a multidimensional search domain, thereby assuming no a priori knowledge of the chemical reactions. This autonomous self-optimizing system allowed fast and efficient optimizations of the chemical steps leading to carpanone. This contribution is the first example of a multistep synthesis where all discrete steps were optimized wit...
TL;DR: A new family of coumarin-based fluorophores, nicknamed COUPY, with promising photophysical properties, including emission in the far-red/near-infrared (NIR) region, large Stokes shifts, high photostability, and excellent brightness are introduced.
Abstract: Among the palette of previously described fluorescent organic molecules, coumarins are ideal candidates for developing cellular and molecular imaging tools due to their high cell permeability and minimal perturbation of living systems. However, blue-to-cyan fluorescence emission is usually difficult in in vivo applications due to the inherent toxicity and poor tissue penetration of short visible light wavelengths. Here, we introduce a new family of coumarin-based fluorophores, nicknamed COUPY, with promising photophysical properties, including emission in the far-red/near-infrared (NIR) region, large Stokes shifts, high photostability, and excellent brightness. COUPY fluorophores were efficiently synthesized in only three linear synthetic steps from commercially available precursors, with the N-alkylation of a pyridine moiety being the key step at the end of the synthetic route, as it allows for the tuning of the photophysical properties of the resulting dye. Owing to their low molecular weights, COUPY dyes show excellent cell permeability and accumulate selectively in nucleoli and/or mitochondria of HeLa cells, as their far-red/NIR fluorescence emission is easily detected at a concentration as low as 0.5 μM after an incubation of only 20 min. We anticipate that these coumarin scaffolds will open a way to the development of novel coumarin-based far-red to NIR emitting fluorophores with potential applications for organelle imaging and biomolecule labeling.
TL;DR: A novel electrophilic thiocyanation reaction was achieved with high yields (up to 99%) and the potential recycling of Saccharin, the wide scope of substrates, and the mild reaction conditions made this protocol much more practical.
Abstract: N-Thiocyanatosaccharin (R1) was readily prepared from the sweet additive Saccharin in two steps with a 71% overall yield. By applying this new reagent to diverse nucleophiles such as benzothiophenes, indoles, oxindoles, aromatic amines, phenols, β-keto carbonyl compounds, and aromatic ketones, a novel electrophilic thiocyanation reaction was achieved with high yields (up to 99%). The potential recycling of Saccharin, the wide scope of substrates, and the mild reaction conditions made this protocol much more practical.
TL;DR: Two environmentally benign methods for the synthesis of quinazolines via acceptorless dehydrogenative coupling of 2-aminobenzylamine with benzyl alcohol and benzonitrile and tetraaza macrocyclic ligands are reported.
Abstract: Two environmentally benign methods for the synthesis of quinazolines via acceptorless dehydrogenative coupling of 2-aminobenzylamine with benzyl alcohol (Path A) and 2-aminobenzylalcohol with benzonitrile (Path B), catalyzed by cheap, earth abundant and easy to prepare nickel catalysts, containing tetraaza macrocyclic ligands (tetramethyltetraaza[14]annulene (MeTAA) or 6,15-dimethyl-8,17-diphenyltetraaza[14]annulene (MePhTAA)) are reported. A wide variety of substituted quinazolines were synthesized in moderate to high yields starting from cheap and easily available starting precursors. A few control reactions were performed to understand the mechanism and to establish the acceptorless dehydrogenative nature of the catalytic reactions.
TL;DR: Utilizing a recently discovered precatalyst, Pd-catalyzed Suzuki-Miyaura and Buchwald-Hartwig reactions involving cleavage of the C(acyl)-O bond of aryl esters that proceed under mild conditions are reported.
Abstract: Esters are valuable electrophiles for cross-coupling due to their ubiquity and ease of synthesis. However, harsh conditions are traditionally required for the effective cross-coupling of ester substrates. Utilizing a recently discovered precatalyst, Pd-catalyzed Suzuki–Miyaura and Buchwald–Hartwig reactions involving cleavage of the C(acyl)–O bond of aryl esters that proceed under mild conditions are reported. The Pd(II) precatalyst is highly active because it is reduced to the Pd(0) active species more rapidly than previous precatalysts.
TL;DR: There has been an increasing push in industry and academia to replace reactions run in traditional organic solvents with alternatives that function in aqueous media.
Abstract: Chemical reactions in water underpin the very existence of life But to synthetic chemists, water is usually considered an enemy, lurking in the shadows, waiting to reduce yields and destroy reproducibility Indeed, chemists often take great pains to exclude even traces of water from their reaction media, and if water does make an appearance in a synthetic procedure, it is only in the course of workup Instead, fine-chemical syntheses tend to use petroleum-derived solvents, which contribute to a vast pool of toxic waste,(1,2) and water-sensitive reactions, which complicate process development and oftentimes create safety hazards(3) Thus, there has been an increasing push in industry and academia to replace reactions run in traditional organic solvents with alternatives that function in aqueous media
TL;DR: The first catalytic asymmetric dearomative [3 + 2] cycloaddition of 3-nitroindoles with vinylcyclopropanes has been established, which constructed chiral cyclopenta[b]indoline scaffolds in generally high enantioselectivities.
Abstract: The first catalytic asymmetric dearomative [3 + 2] cycloaddition of 3-nitroindoles with vinylcyclopropanes has been established, which constructed chiral cyclopenta[b]indoline scaffolds in generally high enantioselectivities (up to 97% ee) This reaction also represents the first application of all-carbon 1,3-dipoles in catalytic asymmetric dearomative [3 + 2] cycloadditions of 3-nitroindoles This approach will not only advance the catalytic asymmetric dearomatization reactions of electron-deficient indoles but also provide an efficient method for constructing chiral cyclopenta[b]indoline scaffolds
TL;DR: The discovery, development and applications of conceptually orthogonal strategies to target-directed synthesis are discussed, with a particular emphasis given to those methods developed in the laboratory.
Abstract: The transition metal-catalyzed allylic substitution reaction is a particularly versatile method for the construction of carbon–carbon and carbon–heteroatom bonds In this regard, the rhodium-catalyzed variant has emerged as a powerful method for the regioselective and stereospecific allylic substitution of chiral nonracemic secondary and tertiary allylic carbonates with a variety of carbon- and heteroatom-based nucleophiles In addition, recent developments have made the analogous enantioselective process possible using prochiral nucleophiles with achiral allylic electrophiles, which represents a significant advance in this area In this Perspective, the discovery, development and applications of these conceptually orthogonal strategies to target-directed synthesis are discussed, with a particular emphasis given to those methods developed in our laboratory
TL;DR: The synthetic utility of this process was demonstrated through direct reductive amination and functionalization of the carbon-carbon double bond of the desired products.
Abstract: Asymmetric dearomative [3 + 2] cycloaddition reactions of 3-nitroindoles with vinyl aziridine and vinyl cyclopropanes have been respectively successfully developed in the presence of a chiral box/Pd(0) complex. A series of enantiomerically enriched 3a-nitro-hexahydropyrrolo[2,3-b]indole and 8b-nitrohexahydrocyclopenta[b]indole derivatives containing three contiguous chiral centers are smoothly obtained in high yields with satisfactory regio-, chemo-, and enantioselectivity. Remarkably, the synthetic utility of this process was demonstrated through direct reductive amination and functionalization of the carbon–carbon double bond of the desired products.
TL;DR: A metal-free visible-light-promoted C(sp3)-C(sp2) cross-dehydrogenative coupling between tetrahydroisoquinoline and imidazo[1,2- a]pyridine has been developed to afford 3-substituted imidazopyridines using a catalytic amount of rose bengal as photosensitizer under aerobic conditions.
Abstract: A metal-free visible-light-promoted C(sp3)-C(sp2) cross-dehydrogenative coupling between tetrahydroisoquinoline and imidazo[1,2- a]pyridine has been developed to afford 3-substituted imidazopyridines using a catalytic amount of rose bengal as photosensitizer under aerobic conditions. The present methodology is also applicable to imidazo[1,2- a]pyrimidine, indolizine, indole, and pyrrole as well as N, N-dimethyl aniline. Wide substrates scope, use of organo photocatalyst, metal-free, and mild reaction conditions are the attractive features of this methodology.
TL;DR: This protocol has not only fulfilled the task of developing cyclization reactions of para-quinone methide derivatives but also provided an efficient method for constructing chromene and xanthene scaffolds.
Abstract: The first cyclization of para-quinone methide derivatives with alkynes was established by utilizing the [4 + 2] reaction of ortho-hydroxyphenyl-substituted para-quinone methides with ynones or benzyne, which efficiently constructed the scaffolds of chromene and xanthene in high yields (up to 88%). This protocol has not only fulfilled the task of developing cyclization reactions of para-quinone methide derivatives but also provided an efficient method for constructing chromene and xanthene scaffolds.
TL;DR: A series of novel ruthenium(II) complexes supported by a symmetrical NNN ligand exhibited good performance in transfer hydrogenation to form new C-C bonds using alcohols as the alkylating agents, generating water as the only byproduct.
Abstract: A series of novel ruthenium(II) complexes supported by a symmetrical NNN ligand were prepared and fully characterized. These complexes exhibited good performance in transfer hydrogenation to form new C–C bonds using alcohols as the alkylating agents, generating water as the only byproduct. A broad range of substrates, including (hetero)aryl- or alkyl-ketones and alcohols, were well tolerated under the optimized conditions. Notably, α-substituted methylene ketones were also investigated, which afforded α-branched steric hindrance products. A potential application of α-alkylation of methylene acetone to synthesize donepezil was demonstrated, which provided the desired product in 83% yield. Finally, this catalytic system could be applied to a one-pot double alkylation procedure with sequential addition of two different alcohols. The current protocol is featured with several characteristics, including a broad substrate scope, low catalyst (0.50 mol %) loadings, and environmental benignity.
TL;DR: The well-defined heavy rare-earth ytterbium iodide complex 1 (L2YbI) has been successfully employed as an efficient catalyst for the hydroboration of aldehydes and ketones with pinacolborane (HBpin) at room temperature.
Abstract: The well-defined heavy rare-earth ytterbium iodide complex 1 (L2YbI) has been successfully employed as an efficient catalyst for the hydroboration of a wide range of aldehydes and ketones with pinacolborane (HBpin) at room temperature. The protocol requires low catalyst loadings (0.1–0.5 mol %) and proceeds rapidly (>99% conversion in <10 min). Additionally, catalyst 1 shows a good functional group tolerance even toward the hydroxyl and amino moieties and displays chemoselective hydroboration of aldehydes over ketones under mild conditions.
TL;DR: Diaporindenes A-D, four unusual 2,3-dihydro-1 H-indene isomers, a novel isoprenylisobenzofuran A, and a new benzophenone derivative tenellone D (11), together with four known biogenetic agents, were all separated from the endophytic fungus Diaporthe sp.
Abstract: Diaporindenes A-D (1-4), four unusual 2,3-dihydro-1 H-indene isomers, a novel isoprenylisobenzofuran A (5), two new isoprenylisoindole alkaloids diaporisoindoles D and E (6 and 7), and a new benzophenone derivative tenellone D (11), together with four known biogenetic agents (8-10 and 12), were all separated from the endophytic fungus Diaporthe sp. SYSU-HQ3 guided by ultraperformance liquid chromatography high-resolution mass spectrometry. The absolute configurations of 1-7 and 11 were defined by X-ray diffraction, quantum chemical calculations, and spectroscopic analysis. Diaporindenes A-D (1-4) possessed an unprecedented chemical skeleton featuring a 2,3-dihydro-1 H-indene ring and a 1,4-benzodioxan moiety. All of the isolates (1-12) were tested for their inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 1-5, 8, and 9 were found to exhibit significant inhibitory effects against nitric oxide production with IC50 values from 4.2 to 9.0 μM and SI values from 3.5 to 6.9. In addition, the structure-activity relationships of all compounds were summarized.
TL;DR: The hydroboration of ketones, aldehydes, and imines with pinacolborane (HBpin) has been achieved using the recyclable CP catalyst in the presence of an air-stable activator.
Abstract: Highly effective hydroboration precatalyst is developed based on a cobalt(II)-terpyridine coordination polymer (CP). The hydroboration of ketones, aldehydes, and imines with pinacolborane (HBpin) has been achieved using the recyclable CP catalyst in the presence of an air-stable activator. A wide range of substrates containing polar C═O or C═N bonds have been hydroborated selectively in excellent yields under ambient conditions.
TL;DR: The 3-sulfonyl indenones synthesized through the newly developed copper-catalyzed radical cascade cyclization strategy were found to own typical aggregation-induced emission (AIE) properties, showing orange to red emission with large Stokes shift (more than 135 nm).
Abstract: An efficient copper-catalyzed radical cascade cyclization strategy was developed, by which a wide variety of 3-sulfonyl substituted indenones were prepared in one pot via reaction of 2-alkynylbenzonitriles with sulfonyl hydrazides in the presence of TBHP and CuI under mild reaction conditions. Much more importantly, the 3-sulfonyl indenones, synthesized through our newly developed copper-catalyzed radical cascade cyclization strategy, were found to own typical aggregation-induced emission (AIE) properties, showing orange to red emission with large Stokes shift (more than 135 nm). In addition, such newly found AIEgens could be successfully used in live cell imaging, exhibiting excellent biocompatibility and application potential.
TL;DR: A novel C-S bond cleavage and reconstruction strategy for the synthesis of thiocyanates through direct photocatalytic S-H bond cyanation from thiols and inorganic thiOCyanate salts is reported.
Abstract: Herein we report a novel C–S bond cleavage and reconstruction strategy for the synthesis of thiocyanates through direct photocatalytic S–H bond cyanation from thiols and inorganic thiocyanate salts. In our strategy, the unprecedented example of cutting off C–S bond of SCN– to deliver the green “CN” sources is demonstrated. This transformation features nontoxic and inexpensive “CN” sources, available starting materials, metal-/base-/ligand-/peroxide-free, high step economy and mild conditions. It leads to the construction of various thiocyanates and some medicinally and biologically active thiocyanate-containing molecules.
TL;DR: A visible-light-mediated decarboxylative cyclization of N-acyloxylphthalimides with vinyl azides has been developed under metal-free conditions, providing a facile and efficient access to substituted phenanthridines.
Abstract: A visible-light-mediated decarboxylative cyclization of N-acyloxylphthalimides with vinyl azides has been developed under metal-free conditions. This protocol features mild conditions, a broad substrate scope, and an excellent functional group tolerance, thus providing a facile and efficient access to substituted phenanthridines. Control experiments revealed that the reaction proceeded via a radical process.
TL;DR: A new aerobic cross-dehydrogenative coupling of C-H and S-H to synthesize aryl sulfides in water, utilizing CoPcS as the catalyst and O2 as the oxidant is developed, showing great tolerance of a wide range of substrates.
Abstract: Organosulfides have great significance and value in synthetic and biological chemistry. To establish a versatile and green methodology for C–S bond generation, we successfully developed a new aerobic cross-dehydrogenative coupling of C–H and S–H to synthesize aryl sulfides in water, utilizing CoPcS as the catalyst and O2 as the oxidant. This protocol shows great tolerance of a wide range of substrates. A large variety of organosulfur compounds were produced in modest to excellent yields.